Late Breaking Abstract - Title: Air-born allergens modulate the immunological lung microenvironment

Introduction: natural air-born allergens can directly modulate the activity of dendritic cells (DCs) by enhancing ST2 expression and the IL-33-induced Th2 polarizing activity (PMID: 23608732), but what is their role in modify the immunological microenvironment of lung is largely unknown. The study evaluates the functional relevance of respiratory cells targeted modulatory activity by the major allergen Der f 1 and its mechanism of action. Authors: Afferni C, Lucarini V., Buccione C, Ziccheddu G., Schiavoni G., Mattei F. Methods: QRT-PCR, FACS analysis, ELISA. Results: natural Der f 1 stimulated the human type II pneumocytes-derived A549 cells to up-regulate the Th2-cells chemoattracting CCL20 mRNA, eosinophils chemoattracting CCL5 mRNA, IL13 mRNA and to release the Th2-polarizing IL33 cytokine. Of note IL33 chemoattracts mouse DCs as efficiently as CCL21, even if IL33 pretreated DCs migrated to higher extension toward IL33. We observed that final maturing bone-marrow derived mouse eosinophils by IL33 enable these cells to up-regulate IL13 and IL4 mRNA, to release the relative cytokines and to up-regulate the activation marker CD69. Conclusion: Der f 1 modulates the lung innate immunity by its effects on the alveolus lining cells, which are at the interface between the external environment and the mucosal immune system. In fact IL33 targeted DCs together with eosinophils-derived IL13 and IL4, and lung recruited Th2 cells could be sufficient for the sensitizing phase of the allergic response (PMID:23169007) and could be able to sustain the chronicity of an ongoing respiratory disease. The results are novel, important both for allergy immunotherapy and health impact of indoor environment.